Genetic Variant EVC:c.1099-19T>C (chr4-5752817-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153717.3(EVC):c.1099-19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 1,612,372 control chromosomes in the GnomAD database, including 148,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11572 hom., cov: 33)

Exomes 𝑓: 0.43 ( 136447 hom. )

Consequence

EVC
NM_153717.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.802

Publications

13 publications found

Variant links:

Genes affected

EVC (HGNC:3497): (EvC ciliary complex subunit 1) This gene encodes a protein containing a leucine zipper and a transmembrane domain. This gene has been implicated in both Ellis-van Creveld syndrome (EvC) and Weyers acrodental dysostosis. [provided by RefSeq, Jul 2008]

EVC links:

CRMP1 (HGNC:2365): (collapsin response mediator protein 1) This gene encodes a member of a family of cytosolic phosphoproteins expressed exclusively in the nervous system. The encoded protein is thought to be a part of the semaphorin signal transduction pathway implicated in semaphorin-induced growth cone collapse during neural development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

CRMP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 4-5752817-T-C is Benign according to our data. Variant chr4-5752817-T-C is described in ClinVar as Benign. ClinVar VariationId is 262764.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153717.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EVC	NM_153717.3	MANE Select	c.1099-19T>C	intron	N/A	NP_714928.1	P57679
EVC	NM_001306090.2		c.1099-19T>C	intron	N/A	NP_001293019.1
EVC	NM_001306092.2		c.1099-19T>C	intron	N/A	NP_001293021.1	E9PCN4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EVC	ENST00000264956.11	TSL:1 MANE Select	c.1099-19T>C	intron	N/A	ENSP00000264956.6	P57679
EVC	ENST00000509451.1	TSL:1	c.1099-19T>C	intron	N/A	ENSP00000426774.1	E9PCN4
EVC	ENST00000861182.1		c.1099-19T>C	intron	N/A	ENSP00000531241.1

Frequencies

GnomAD3 genomes

AF:

0.373

AC:

56686

AN:

152032

Hom.:

11576

Cov.:

show subpopulations

Gnomad AFR

AF:

0.208

Gnomad AMI

AF:

0.393

Gnomad AMR

AF:

0.459

Gnomad ASJ

AF:

0.481

Gnomad EAS

AF:

0.316

Gnomad SAS

AF:

0.282

Gnomad FIN

AF:

0.439

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.448

Gnomad OTH

AF:

0.376

GnomAD2 exomes

AF:

0.408

AC:

102352

AN:

250600

AF XY:

0.404

show subpopulations

Gnomad AFR exome

AF:

0.204

Gnomad AMR exome

AF:

0.481

Gnomad ASJ exome

AF:

0.475

Gnomad EAS exome

AF:

0.313

Gnomad FIN exome

AF:

0.442

Gnomad NFE exome

AF:

0.450

Gnomad OTH exome

AF:

0.433

GnomAD4 exome

AF:

0.427

AC:

623859

AN:

1460222

Hom.:

136447

Cov.:

AF XY:

0.423

AC XY:

307433

AN XY:

726546

show subpopulations

African (AFR)

AF:

0.198

AC:

6619

AN:

33466

American (AMR)

AF:

0.480

AC:

21482

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.482

AC:

12604

AN:

26126

East Asian (EAS)

AF:

0.300

AC:

11914

AN:

39694

South Asian (SAS)

AF:

0.290

AC:

24977

AN:

86228

European-Finnish (FIN)

AF:

0.443

AC:

23647

AN:

53392

Middle Eastern (MID)

AF:

0.388

AC:

2236

AN:

5768

European-Non Finnish (NFE)

AF:

0.446

AC:

495333

AN:

1110480

Other (OTH)

AF:

0.415

AC:

25047

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

19115

38230

57346

76461

95576

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14774

29548

44322

59096

73870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.373

AC:

56699

AN:

152150

Hom.:

11572

Cov.:

AF XY:

0.369

AC XY:

27474

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.208

AC:

8637

AN:

41548

American (AMR)

AF:

0.459

AC:

7018

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.481

AC:

1670

AN:

3470

East Asian (EAS)

AF:

0.315

AC:

1622

AN:

5146

South Asian (SAS)

AF:

0.283

AC:

1363

AN:

4818

European-Finnish (FIN)

AF:

0.439

AC:

4644

AN:

10586

Middle Eastern (MID)

AF:

0.432

AC:

127

AN:

294

European-Non Finnish (NFE)

AF:

0.448

AC:

30469

AN:

67976

Other (OTH)

AF:

0.375

AC:

791

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1816

3633

5449

7266

9082

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

536

1072

1608

2144

2680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.432

Hom.:

19901

Bravo

AF:

0.369

Asia WGS

AF:

0.273

AC:

950

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Ellis-van Creveld syndrome (2)

not provided (2)

Curry-Hall syndrome (1)

Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.14

(source)

DANN

Benign

0.60

PhyloP100

-0.80

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over